Fecal short-chain fatty acids of very-low-birth-weight preterm infants fed expressed breast milk or formula.

OBJECTIVES: In preterm infants, the metabolic responses of gastrointestinal (GI) bacteria to different diets are poorly understood despite the possible effects on GI health. Therefore, we tested the hypothesis that diet influences bacterial metabolism by measuring short-chain fatty acids (SCFAs) in stool samples from very-low-birth-weight (VLBW) preterm infants without GI disorder as surrogate biomarkers of bacterial metabolism. METHODS: Ion chromatography was used to measure fecal SCFAs (acetate, formate, propionate, butyrate, and isobutyrate), lactate, and chloride in fresh stool samples collected from 32 preterm infants (without major congenital anomalies, GI disorders, or a recent history of antibiotic administration and on full feed of either expressed maternal breast milk [EBM; n = 13] or a formula for preterm infants [Similac Special Care Formula; preterm formula, PTF; n = 19]). RESULTS: The mean birth weight was 972 g, the mean gestational age was 27 weeks, and the mean postnatal age at first stool sample was 36 days. When adjusted for gestational age, the stools of EBM infants had higher concentrations (micromoles per gram of stool) of total SCFA (128 vs 68; P = 0.002), acetate (41 vs 13; P = 0.005), propionate (15.1 vs 4.4; P = 0.003), and chloride (21,814 vs 10,652; P = 0.02). Interactions between postnatal age and diet were detected for lactate (P = 0.05), propionate (P = 0.03), and butyrate (P = 0.03). CONCLUSIONS: Diets fed to VLBW preterm infants influence fecal SCFA profiles, and hence the metabolism of the GI bacteria, and potentially the health of preterm infants. The responses of bacterial metabolism to diet are influenced with postnatal age and gestational age at birth.

Modeling Uhthoff's phenomenon in MS patients with internuclear ophthalmoparesis.

OBJECTIVE: The goal of this investigation was to demonstrate that internuclear ophthalmoparesis (INO) can be utilized to model the effects of body temperature-induced changes on the fidelity of axonal conduction in multiple sclerosis (Uhthoff's phenomenon). METHODS: Ocular motor function was measured using infrared oculography at 10-minute intervals in patients with multiple sclerosis (MS) with INO (MS-INO; n = 8), patients with MS without INO (MS-CON; n = 8), and matched healthy controls (CON; n = 8) at normothermic baseline, during whole-body heating (increase in core temperature 0.8 degrees C as measured by an ingestible temperature probe and transabdominal telemetry), and after whole-body cooling. The versional disconjugacy index (velocity-VDI), the ratio of abducting/adducting eye movements for velocity, was calculated to assess changes in interocular disconjugacy. The first pass amplitude (FPA), the position of the adducting eye when the abducting eye achieves a centrifugal fixation target, was also computed. RESULTS: Velocity-VDI and FPA in MS-INO patients was elevated (p < 0.001) following whole body heating with respect to baseline measures, confirming a compromise in axonal electrical impulse transmission properties. Velocity-VDI and FPA in MS-INO patients was then restored to baseline values following whole-body cooling, confirming the reversible and stereotyped nature of this characteristic feature of demyelination. CONCLUSIONS: We have developed a neurophysiologic model for objectively understanding temperature-related reversible changes in axonal conduction in multiple sclerosis. Our observations corroborate the hypothesis that changes in core body temperature (heating and cooling) are associated with stereotypic decay and restoration in axonal conduction mechanisms.

Pharmacokinetic and pharmacodynamic issues in the treatment of bacterial infectious diseases.

This review outlines some of the many factors a clinician must consider when selecting an antimicrobial dosing regimen for the treatment of infection. Integration of the principles of antimicrobial pharmacology and the pharmacokinetic parameters of an individual patient provides the most comprehensive assessment of the interactions between pathogen, host, and antibiotic. For each class of agent, appreciation of the different approaches to maximize microbial killing will allow for optimal clinical efficacy and reduction in risk of development of resistance while avoiding excessive exposure and minimizing risk of toxicity. Disease states with special considerations for antimicrobial use are reviewed, as are situations in which pathophysiologic changes may alter the pharmacokinetic handling of antimicrobial agents.

Effects of past abuse experiences on children's eyewitness memory.

Relations between child maltreatment and children's eyewitness memory were examined. A matched sample of abused and nonabused 3- to 10-year-old children (n = 70) participated in a play session with an unfamiliar adult and were interviewed about the interaction 2 weeks later. Consistent with results from previous research, older compared to younger children's reports were more complete and accurate. Abused and nonabused children performed similarly with several exceptions: Nonabused children were more accurate in answering specific questions, made fewer errors in identifying the unfamiliar adult in a photo identification task, and (at least for younger boys) freely recalled more information. Most effects remained when group differences in IQ and behavioral symptomology were statistically controlled. Importantly, abused and nonabused children did not differ in their accuracy or suggestibility in response to questions that were relevant to abusive actions. Among abused children, however, those who suffered more severe sexual abuse made more omission errors to specific abuse-relevant questions. Contributions to psychological theory and legal implications for understanding children's eyewitness memory and testimony are discussed.

Multiple isoforms of porcine aromatase are encoded by three distinct genes.

Cytochrome P450 aromatase, a product of the CYP 19 gene and the terminal enzyme in the estrogen biosynthetic pathway, is synthesized by the ovary, endometrium, placenta, and peri-implantation embryos in the pig and other mammals, albeit to varying levels, implying its functional role(s) in pregnancy events. The aromatase produced by the pig tissues exists as three distinct isoforms (type I - ovary, type II - placenta, and type III - embryo), with presumed differences in substrate specificities, expression levels, activity, and mode of regulation. In order to delineate the molecular mechanisms whereby estrogen synthesis is regulated in these diverse tissues, the present study examined if these aromatase isoforms represent products of multiple genes or of a single gene via complex splicing mechanisms. Porcine genomic DNA from a single animal was used as a template in the polymerase chain reaction (PCR) to amplify isoform-specific sequences corresponding to exons 4 and 7, respectively. Nucleotide sequence analysis of the generated fragments revealed the presence of only clones corresponding to the three known aromatase types. Screening a porcine Bacterial Artificial Chromosome (BAC) library for aromatase gene by PCR yielded a single clone approximately 80 kb in length. Southern blot analysis, using probes specific for exons 1A-1B, 2-3, 4-9, and 10 sequences indicated that the BAC genomic clone contains the entirety of the coding exons as well as the proximal promoter region. Sequence analysis of the fragment generated with exon 4 primers determined that this BAC clone contains only the type II gene. The presence and relative orientation of the untranslated 5'- exons 1A and 1B, previously demonstrated for the type III isoform were evaluated in the BAC clone and genomic DNA by PCR. The 265 bp fragment generated from both PCR reactions was confirmed by sequence analysis to contain exons 1A and 1B that are located contiguous to each other and separated by only three bp. A diagnostic procedure for typing aromatase isoforms was developed, based on the presence of specific restriction sites within isoform-specific exons. The use of this protocol confirmed the existence of only three aromatase isoforms in the porcine genome and indicated changes in aromatase types expressed by the uterine endometrium as a function of pregnancy stage. The presence of distinct genes encoding each of the aromatase isoform predicts important differences in the mechanisms underlying the molecular evolution and regulation of porcine aromatase, unique from those of other mammals, and suggests a critical role for P450 aromatase steroidal products in uterine functions related to pregnancy events.

Jurors' reactions to satanic ritual abuse allegations.

OBJECTIVE: Some of the most highly publicized child sexual abuse trials of this century have involved bizarre allegations of satanic ritual abuse, yet little is known about jurors' reactions to ritual abuse claims. We investigated how jurors' judgements of defendant guilt and witness credibility are affected by the presence or absence of satanic ritual abuse allegations. METHOD: Two hundred forty-three mock jurors rendered judgments about a case involving childhood sexual abuse allegations made by either a 5-year-old child or a 30-year-old adult survivor. The presence or absence of satanic ritual abuse allegations was varied between subjects. Jurors' religiosity was measured. RESULTS: Although jurors were significantly less likely to believe the satanic ritual allegations than other case details, they were as likely to vote guilty and to believe the victim in satanic as in nonsatanic cases. Victim age had no significant effect on mock jurors' judgments, but there were marked individual differences in decisions: When the allegations involved satanic ritual abuse, religious jurors were more likely than less religious jurors to believe the victim. Further, across all conditions, women made more pro-victim judgements than did men. CONCLUSIONS: Our findings suggest that highly bizarre details may be discounted by jurors (particularly less religious jurors), but that jurors may set aside their skepticism of satanic ritual details and make judgments about child sexual abuse cases based on their perceptions of the credibility of nonsatanic allegations of harm. Whether or not this is an accurate approach to decision-making in these cases remains an empirical question.

Liquid ventilation in premature lambs: uptake, biodistribution and elimination of perfluorodecalin liquid.

Perfluorochemical (PFC) liquids are biologically inert and nonbiotransformable substances that, when used as breathing medium, may be transported across the lung epithelium in small quantities, distributed throughout the body, and ultimately vapourized through the lungs and transpired through the skin. To further evaluate the uptake, biodistribution and elimination of a PFC liquid (perfluorodecalin) in the neonatal population, arterial blood, tissue and expired gas samples were obtained from preterm lambs (105-114 days gestation). Two groups of premature lambs were studied: Group I (n = 4) lambs were liquid ventilated from birth for 1 h and killed without exposure to gas ventilation (GV) and Group II (n = 5) lambs were liquid ventilated for 1 h followed by up to 2 h of GV. Samples were analysed by electron-capture gas chromatography and data were expressed in nl of PFC/ml of blood or gas and nl of PFC/gm tissue. During liquid ventilation and subsequent GV, PFC blood levels significantly increased (P < 0.001) from baseline control levels (0.007 +/- 0.001 SE nl PFC/ml blood) to a high of 2.95 +/- 1.03 SE nl PFC/ml blood. Perfluorochemical levels measured in expired gas (Group II) demonstrated a rapid decrease as a function of time of GV. Tissue levels of PFC indicated that uptake of PFC in Group I was significantly different (P < 0.001) than baseline levels and organ dependent; the highest levels were in the lungs (221 +/- 26.2 SE nl PFC/g tissue) and the lowest in the liver (2.24 +/- 1.6 SE nl PFC/g tissue). Comparison of tissue levels of PFC between groups indicated a 34.8% mean decrease across organs in Group II compared with Group I. These data indicate that PFC uptake and elimination is organ dependent and that PFC liquids can be eliminated through the lungs upon return to GV. Sustained PFC blood levels may be related to residual PFC in the organs and lung as well as regional variation in ventilation-perfusion matching upon return to GV.

Hypothalamic control of endocrine thermogenesis.

Hypothalamic and ruminal cooling raised serum thyrotropin (TSH), adrenocorticotropin (ACTH), norepinephrine (NE), and glucose in conscious goats in 20 degree C ambient temperature. Cooling of the preoptic anterior hypothalamus (POAH) for 2 h initially evoked shivering and vasoconstriction, leading to 1.5 degree C rise in rectal temperature (Tr). Pituitary-thyroid activation by POAH cooling was shown by peak rises in TSH of 60% at 40 min, in triiodothyronine (T3) of 54% at 80 min, and in thyroxine (T4) of 40% at 140 min. At 60 min, ACTH and NE peaked at 57 and 65%, respectively. TSH, ACTH, and NE declined during the 2nd h of POAH cooling as Tr plateaued; when POAH cooling was stopped, these hormones fell below basal level as vasodilation and panting restored Tr to normal. In contrast to the core hyperthermia evoked by POAH cooling, ruminal intubation with O degree C water (1 liter/10 kg) led to general hypothermia, Tpoah and Tr falling 1.6 degree C at 40 min. Pituitary-thyroid responses were less but ACTH and NE more, compared with POAH cooling. TSH peaked at 37% at 20 min, T3 at 55% at 60 min, and T4 at 18% at 200 min. ACTH peaked at 250% at 30 min and NE at 120% at 20 min. Thermosensitive neurons in the POAH seem to mediate more sensitive and complete control over TSH than over ACTH, or NE release, whereas extrahypothalamic core thermosensitivity (e.g., brain stem, spinal cord, abdomen) may influence ACTH and NE more than TSH release.